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Original Research

Applied Medical Research


www.scopemed.org
DOI: 10.5455/amr.20150412074909

Cutaneous tuberculosis:
Aclinicopathological study of 50cases
from a tertiary care referral hospital
Rajpal Singh Punia1, Phiza Aggarwal1, Reetu Kundu1, Harsh Mohan1,
Mala Bhalla2, Deepak Aggarwal3
Department of
Pathology, Government
Medical College and
Hospital, Chandigarh,
India, 2Department
of Dermatology and
Venereology, Government
Medical College and
Hospital, Chandigarh,
India, 3Department of
Pulmonary Medicine,
Government Medical
College and Hospital,
Chandigarh, India

Address for correspondence:


Reetu Kundu, Department
of Pathology, Government
Medical College and
Hospital, Chandigarh, India.
E-mail: reetukundu@gmail.
com
Received: March 31, 2015
Accepted: April 12, 2015
Published: April 21, 2015

ABSTRACT
Background: Tuberculosis (TB) is a health problem worldwide. Cutaneous TB comprises a small fraction of
all clinical forms of TB. Objective: The purpose of this study was to assess the disease pattern of cutaneous
TB in an Asian country. Materials and Methods: Totally, 50 cases of cutaneous TB were diagnosed on
histopathology in a tertiary care hospital over a period of 7 years. Relevant clinical details and available
laboratory findings were correlated. Results: The patients ranged from 4 to 78 years with 26 males and
24 females. Neck was the most common site. 22 (44%) cases presented with erythematous plaques followed
by papules in 9 (18%) cases. Classical epithelioid cell granulomas with Langhans giant cells were found in
46 (92%) patients, while caseation necrosis was seen in 18 (36%). On Ziehl-Neelsen staining, acid fast bacilli
were demonstrated in 6 (12%). 24 (48%) patients were diagnosed lupus vulgaris, 11 (22%) scrofuloderma,
4 (8%) TB verrucosa cutis, 1 (2%) TB cutis orificialis, and 10 (20%) TB non-specific type. Conclusion: Lupus
vulgaris is a most common presentation of cutaneous TB. Caseating epithelioid cell granulomas with or without
positive Ziehl-Neelsen stain constitute the classical picture. Knowledge of different histopathological features
and their variation is important for an accurate diagnosis.

KEY WORDS: Cutaneous, granuloma, histopathology, tuberculosis, Ziehl-Neelsen stain

INTRODUCTION
India is the country with highest tuberculosis (TB) burden
in the world with 40% of population being infected with
Mycobacterium TB. Not only in India, TB remains a worldwide
health problem. In 2012, 8.6 million people fell ill with TB and
1.3 million died from it, including 3,20,000 people who were
human immunodeficiency virus (HIV) positive [1]. Pulmonary
TB is the most common form of TB, that being infectious,
attracts global attention for its adequate control. In the latter
half of the 20th century, TB burden showed a declining trend
with the advent of effective chemotherapy and improvement
in living standards. However, with the emergence of HIV and
rise in multi-drug resistant TB, the incidence started increasing
in the late twentieth century [2].
Cutaneous TB comprises a small fraction (<2%) of incident
cases of all clinical forms of TB [3]. Similar to the pulmonary
104

form, cutaneous TB has also showed an initial decrease in the


incidence from 2% to 0.5% in different Indian studies [4,5].
It is characterized by diverse dermatological manifestations,
as a result of which, its identification and classification purely
on clinical grounds is difficult. Lupus vulgaris, scrofuloderma,
and TB verrucosa cutis are among its most common clinical
presentations. In view of poor bacterial isolation, histopathology
remains the main modality for its diagnosis. Caseating
epithelioid cell granulomas with Langhans type giant cells
in dermis with or without positive Ziehl-Neelsen (ZN) stain
for acid fast bacilli (AFB) constitute the classical picture
of cutaneous TB. However, cutaneous TB is characterized
by variations in the histopathological features including
necrotizing granuloma, poorly formed granuloma, non-specific
inflammatory infiltrate, and absence of caseation which make
its diagnosis difficult [6]. We intend to present our 7 years
retrospective data on cutaneous TB patients discussing their
diverse clinical and histopathological features along with
diagnostic correlation.
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Punia, et al.: Clinicopathologic study of cutaneous tuberculosis

MATERIALS AND METHODS


The present study is a retrospective study comprising of
50 cases of cutaneous TB, which were diagnosed on the basis
of histopathology findings. The study was conducted in the
department of pathology, in a tertiary care hospital. The biopsy
samples were sent from the dermatology department of our
hospital. The ethical clearance was not taken on account of the
retrospective nature of the study.
The case records and histopathology reports of selected TB
patients, diagnosed between 2006 and 2012 were collected.
Different parameters like age, gender distribution, site of
involvement, clinical and microscopic findings, culture for
Mycobacterium TB, AFB positivity among different clinical
types of cutaneous TB were evaluated.

RESULTS
The patients ranged from 4 to 78 years of age (median age:
24 years). 32 patients (64%) were below or equal to the age of
30 years [Table 1]. Of 50 patients, 24 were females. Affected
females were relatively younger than males (median age for
females: 21.5 years; for males: 26 years). The neck was the most
common site followed by face [Table 2]. The majority of patients
with neck involvement had secondary skin involvement due to
draining cold abscess. On evaluating the past history, 2 patients
were old treated cases of pulmonary TB and 1 of skin TB. Three
patients had a past history of trauma at the site of skin TB.
Erythematous plaque was the most common clinical finding
seen in 22 (44%) patients [Figure 1]. 8 (16%) patients had
sinus presentation that was secondary to draining cold abscess.
On histopathological examination, epithelioid cell granulomas
along with Langhans giant cells were seen in 46 (92%) patients
while 4 (8%) cases showed granulomas devoid of giant cells
[Table 3]. Of these four cases, caseation necrosis was seen in
all. Of total 50 patients, caseation necrosis was seen in 18 (36%)
Table 1: Age-wise distribution of cases (n=50)
S. No

Age group (in years)

Number of cases (%)

0-9
10-19
20-29
30-39
40-49
50

5 (10)
11 (22)
16 (32)
6 (12)
7 (14)
5 (10)

1
2
3
4
5
6

patients. On ZN staining, AFB was demonstrated in 6 (12%)


patients. Of these, three cases were of scrofuloderma [Figure 2].
Other causes for granulomatous inflammation were ruled out.
Periodic acid Schiff stain for fungus was negative in all the cases.
A careful search for organisms like leishmania on Giemsa stained
sections was also negative.
Of 50 patients, 24 (48%) patients were diagnosed on
histopathology as lupus vulgaris, 11 (22%) patients
scrofuloderma, 4 (8%) patients as TB verrucosa cutis [Figure 3],
10 (20%) patients were labeled as TB - non-specific type, and
1 (2%) patient was diagnosed as TB cutis orificialis [Table 3].
Median age of presentation for lupus vulgaris was 20 years
with males being more affected than females (16 vs. 8 years).
Face was the most common site of involvement [Figure 4]. In
contrast to lupus vulgaris, scrofuloderma was more common
in females. It was most commonly associated with a draining
sinus due to underlying lymphadenopathy (8 out of 11 cases)
[Figure 5]. 7 patients (64%) of scrofuloderma had evidence
of caseous necrosis in contrast to 5 (21%) patients with lupus
vulgaris. Rest of the 11 cases of scrofuloderma and 19 cases of
lupus vulgaris [Figure 6] showed granulomas without caseation.

Figure 1: Spectrum of clinical appearances of lesions in cutaneous


tuberculosis (n = 50)

Table 2: Site of involvement in cutaneous tuberculosis (n=50)


Site of involvement
Neck
Face (ear, chin, lips)
Trunk (chest and back)
Knee
Foot
Forearm/arm
Axilla
Gluteal and perianal region
Thigh
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Number of cases (%)


10 (20)
9 (18)
8 (16)
6 (12)
6 (12)
4 (8)
3 (6)
3 (6)
1 (2)

Figure 2: Caseating epithelioid cell granulomas in scrofuloderma


(H and E, 200). Inset shows acid-fast bacilli (Ziehl-Neelsen, 1000)
105

Punia, et al.: Clinicopathologic study of cutaneous tuberculosis

Table 3: Composite features in different types of cutaneous tuberculosis (n=50)


Feature
Number of cases
Median age (years)
Male-female ratio
Most common site involved
Histopathology
Epidermis
Hypertrophy
Atrophy
Ulceration
Dermis
Granuloma type
Location
Langhans giant cells
Inflammatory infiltrate
Abscess formation
Caseation necrosis
AFB positivity

Lupus vulgaris (%)

Scrofuloderma (%)

Tuberculosis
verrucosa cutis (%)

Tuberculosis cutis
orificialis (%)

Tuberculosis,
non-specific (%)

24 (48)
20
2:1
Face, 7 (29.2)

11 (22)
25
1:2.6
Neck, 5 (45.5)

4 (8)
29.5
1:1
Foot, 3 (75)

1 (2)
33
Face, 1 (100)

10 (20)
30.5
1: 1.66
Lower limb, 4 (40)

18 (75)
2 (8.3)
4 (16.7)

2 (18.2)
1 (9.1)
8 (72.7)

4 (100)
-

1 (100)

3 (30)
2 (20)
5 (50)

Tuberculoid
Upper dermis, 20 (83.3)
23 (95.8)
Lymphocytic, 21 (87.5)
Absent
5 (20.8)
None

Tuberculoid
Entire dermis, 9 (81.8)
10 (90.9%)
Neutrophilic, 9 (81.8)
10 (90.9)
7 (63.6)
3 (27.3)

Tuberculoid
Mid dermis, 3 (75)
4 (100)
Neutrophilic, 3 (75)
1 (25)
3 (75)
None

Tuberculoid
Entire dermis, 1 (100)
1 (100)
Mixed, 1 (100)
1 (100)
1 (100)
1 (100)

Ill-defined
Variable
8 (80)
Variable
Variable
2 (20)
2 (20)

AFB: Acid fast bacilli

Figure 3: Hyperkeratotic acanthotic epidermis with epithelioid cell


granulomas (black arrow) in tuberculosis verrucosa cutis (H and
E, 100). Inset shows Langhans giant cells (H and E, 400)

Figure 5: Scrofuloderma showing sinus tracts with onset of healing in


response to anti-tubercular treatment

Figure 4: Ulcerative lesion of lupus vulgaris on face

Figure 6: Histopathology of lupus vulgaris showing non-caseating


epithelioid cell granuloma in the upper dermis (H and E, 200)

In 42 patients, the clinical and histopathological diagnosis was


similar with a positive correlation of 84%. Of these 42 patients,

22 patients had more than one differential diagnosis made


on clinical grounds, which was later on confirmed as TB, on

106

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Punia, et al.: Clinicopathologic study of cutaneous tuberculosis

histopathology. All the patients responded to standard therapy


regimes under directly observed therapy short course with
clinical response observed between 2 and 6 weeks of initiation.

DISCUSSION
Cutaneous TB is a rare form of extra-pulmonary TB. Nonspecific and diverse clinical presentation, lack of knowledge,
and histopathological variations are the factors leading to its
under-estimation. Cutaneous TB is a chronic infective disorder
of the skin with an estimated incidence of 0.1% of total patients
visiting dermatology outpatient department [7]. In contrast
to Europe and United States, the incidence is increasing
in countries like India, Pakistan and other parts of Asia and
Africa [8].
The infection is usually caused by Mycobacterium TB and
rarely by Mycobacterium bovis or atypical mycobacteria [9].
As in other forms of TB, current or past history of TB is an
important risk factor for the cutaneous presentation. It also
shows a predilection for sites having skin trauma. In our study,
three patients had a past history of TB and three gave a history of
trauma at the site of infection. Based on the route of infection,
Beyt et al. [10] classified cutaneous TB into exogenous and
endogenous type which are also characterized by distinct clinicohistopathological features.
Cutaneous TB usually involves younger age group. In our study,
54% of patients were in 2nd and 3rd decade of life. Preponderance
for the younger age has also been seen in other studies from
India [11-13]. Skin trauma due to increased physical activity
during younger age as well as contact with active TB cases at
an early age may be the underlying factors for younger age
predilection. However, average age of presentation is higher
in few European studies [14,15]. This can be due to low TB
prevalence in those geographical areas. In Indian subcontinent,
males are more commonly affected than females whereas the
situation is opposite in the western world [3,11,16,17]. However,
male: female ratio was almost equal in our study, the cause of
which cant be elucidated. The neck was the most common
site of involvement in our study followed by the face and trunk.
This was similar to the study by Solis et al., [17] whereas limbs
were the most common sites in other Indian studies [11,13].
The difference is partly due to the variation in the number of
different clinical variants of cutaneous TB seen at different
locations.

Based on the host immune response, the route of inoculation and


previous sensitization, cutaneous TB can present in a number of
clinical forms. Important varieties include TB chancre, miliary
TB of the skin, lupus vulgaris, scrofuloderma, TB verrucosa cutis,
tuberculous gumma, and TB cutis orificialis. Lupus vulgaris is
considered to be the most common clinical variant of cutaneous
TB [12,13,18,19]. It was also the most common form in our study.
However a strong data from India and abroad, points toward
scrofuloderma as the most common type [Table 4] [4,9,17].
Whereas a few researchers have reported TB verrucosa cutis, as
the most frequent form in their studies [12,20].
Lupus vulgaris is a paucibacillary form of cutaneous TB that
usually occurs by endogenous (hematogenous or lymphatic)
spread of infection from an occult focus. It usually affects the
immunocompetent patients. In contrast to our study, females
are more often involved than males in lupus vulgaris [21]. In our
study, out of total 24 patients with lupus vulgaris, around 50%
had face and neck involvement and rest 50% had involvement
of the lower limb and gluteal region. It may be related to
differential route of spread in these groups. Scrofuloderma,
another important clinical variant, occurs by contiguous
(endogenous) spread of infection to the skin from underlying
structures, most commonly lymph node, bone or joint.
Understandably, neck, axilla, chest wall, and groin are the most
probable sites involved. In our study, neck and axilla together
constituted 75% of total cases of scrofuloderma. TB verrucosa
cutis was the other common variant of cutaneous TB seen in
our study. All 4 patients had lesions over their limbs which is
commensurate with the evidence available in literature [11].
Due to non-specific clinicopathological picture and a low
microbiological yield in tissue specimens, diagnosis of cutaneous
TB is difficult as compared to other forms of TB. Most
common differential diagnoses include leprosy, sarcoidosis,
fungal infections, foreign body granulomas, leishmaniasis, and
granulomatous syphilis. Histopathology is the best available
diagnostic modality, which along with corroborative clinical
features can give reasonable diagnostic confirmation. However,
there is a lot of variability in the histopathological features in
skin TB, which makes the job more difficult [4]. Moreover, it
is not always possible to package cutaneous tuberculous lesions
neatly into the specific categories and on occasion these are
reported as non-specific type, particularly in this current era
of profound immunosuppression [22]. This was evident in our
study also, where 10 patients could not be categorized and were
labeled TB - non-specific type.

Table 4: Comparison of features of cutaneous TB among different studies


Feature

Patra et al. [17], 2006

Solis et al. [16], 2012

Chong et al. [18], 1995

Dwari et al. [10], 2010

Present study 2014

Number of cases
Male: Female ratio
Most common age
group (in years)
Most common type
Most common site
AFB positivity (%)

104
2.25:1
5-15 and 16-25

65
1:3.6
-

176
1.2:1
44 (mean age)

50
1.2:1
16-25

50
1:1
20-29

Lupus vulgaris
Lower limbs
0

Scrofuloderma
Neck
13.8

Lupus vulgaris
Head and neck
-

Tuberculosis verrucosa cutis


Limbs and buttock
50.5

Lupus vulgaris
Neck
12

AFB: Acid fast bacilli, TB: Tuberculosis


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Punia, et al.: Clinicopathologic study of cutaneous tuberculosis

Epithelioid cell granulomas with Langhans type giant cells


constitute the classical histopathology of cutaneous TB.
Important variations in the histopathological features seen
among different clinical variants in our study included presence
or absence of caseous necrosis and AFB positivity and wellformed or poorly formed granulomas. To a major extent, these
variations are decided by the degree of host immune reaction.
Hence, on one end of the spectrum histopathological picture
is constituted by epithelioid granulomas with minimal necrosis
and no AFB, indicating high immunity and on the other, the
picture is of extensive necrosis with numerous AFB, indicating
low immunity. In general, lupus vulgaris is seen at the high
immunity end of spectrum, followed by TB verrucosa cutis and
scrofuloderma toward the low immunity end [4]. Of 18 (36%)
cases with caseous necrosis in our study, maximum proportion
of cases was of scrofuloderma and TB verrucosa cutis (63.6% and
75%, respectively), whereas only 20.8% cases of lupus vulgaris
demonstrated caseation. AFB were seen in 12% patients in our
study which was similar to figures achieved by Solis et al. [17]
and Gopinathan et al. [9]. AFB positivity was common in
scrofuloderma and TB orificialis whereas no AFB was detected
in cases of lupus vulgaris.
As already explained, a comprehensive evaluation of clinical
and histopathological findings is the best diagnostic tool for
cutaneous TB. Our study showed a significantly good correlation
(84%) between the clinical and histopathological diagnosis.
However, 8 (16%) patients in our study were detected to have
TB on histopathology, even though the clinician did not suspect
TB. A high index of clinical suspicion is often required.

5.
6.

7.
8.
9.
10.

11.
12.
13.
14.
15.
16.
17.

CONCLUSION
The diagnosis of cutaneous TB is not straightforward as for other
common bacterial infections. In view of the low probability of
bacterial isolation, histopathology remains the best modality
for its diagnosis. Knowledge about histopathological features
of cutaneous TB and their variations among different clinical
variants is important for an accurate diagnosis of this potentially
treatable disease.

18.
19.
20.
21.
22.

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SAGEYA. This is an open access article licensed under the terms


of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted,
noncommercial use, distribution and reproduction in any medium, provided
the work is properly cited.
Source of Support: Nil, Conflict of Interest: None declared.

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